Review POTS, ME/CFS and Long COVID as Neuroimmune Disorders, 2026, Blitshteyn et al

[John Mac]

Full title: Postural Orthostatic Tachycardia Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID as Neuroimmune Disorders

Abstract:
Postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID are heterogeneous disorders with overlapping complex, multi-factorial and multi-systemic pathophysiology.

POTS and ME/CFS are the most common phenotypes of Long COVID that can lead to significant disability and functional impairment. The exact pathophysiologic mechanisms of these disorders alone or in combination are still being investigated, but important mechanistic factors have been identified, such as autonomic dysfunction, immune dysregulation, autoimmunity, mitochondrial dysfunction, cerebral hypoperfusion, and neuroinflammation.

To this end, we believe that these conditions should be viewed as neuroimmune disorders and should be included in the field of neuroimmunology, with its educational curriculum, training, and clinical care pathways. Including these disorders as part of neuroimmunology subspecialty is the key to advancing the science and clinical care of this underserved patient population with these complex and disabling conditions.

POTS, ME/CFS and Long COVID as neuroimmune disorders | ITT

Postural orthostatic tachycardia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome and Long COVID are heterogeneous disorders with overlapping terms.

www.dovepress.com

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[Jonathan Edwards]

Just plain wrong again, unsurprisingly.

 

[Jaybee00]

Just plain wrong again, unsurprisingly

Svetlana disagrees.



Hot off the press: my new paper that moves this field forward and changes the narrative on what #POTS, #MECFS and #LongCOVID are... Neuroimmune Disorders!

The brain and the autonomic nervous system are involved in the immune system regulation.
There is evidence of autoimmunity, immune dysregulation, cerebral hypoperfusion, neuroinflammation and other mechanisms in all three disorders.
#Neuroimmunology is a field that should embrace these disorders: #MultipleSclerosis, the staple of neuroimmunology, used to be called hysterical paralysis before CT and MRI were invented. We're at the same crossroads with these disorders.
These disorders are not "mysterious", "anxiety", "deconditioning," "functional neurologic" etc. etc.
Classifying these disorders as neuroimmune and including them as part of neuroimmunology training is critical.
#PatientCare and lives of millions of people living with these disabling conditions are at stake!

Thanks to my esteemed colleagues and co-authors, Dr. @TaylorDoherty8, immunologist from UC San Diego and Dr. Lawrence Steinman, neuroimmunologist from @StanfordMed, for their support!

 

[DHagen]

Just plain wrong again, unsurprisingly.

Would you be willing to comment on what, specifically, is obviously wrong here? I know there are lots of problems with Dr. Blitshteyn's work and comments elsewhere, and there is much here that is clearly speculative, but are there claims that are demonstrably false?

 

[DMissa]

Would you be willing to comment on what, specifically, is obviously wrong here? I know there are lots of problems with Dr. Blitshteyn's work and comments elsewhere, and there is much here that is clearly speculative, but are there claims that are demonstrably false?

Possibly claims of mechanism in the abstract, when there are currently none that can be made in specific terms with reliable evidence behind them.

 

[Jonathan Edwards]

Would you be willing to comment on what, specifically, is obviously wrong here?

Yup.

important mechanistic factors have been identified, such as autonomic dysfunction, immune dysregulation, autoimmunity, mitochondrial dysfunction, cerebral hypoperfusion, and neuroinflammation.

None of these have been identified convincingly to my knowledge. Certainly nothing has been shown to be an 'important mechanistic factor' even if there are a few data showing differences from normals. The mechanisms are completely unknown.

 

[Jonathan Edwards]

Also:

POTS and ME/CFS are the most common phenotypes of Long COVID that can lead to significant disability and functional impairment.

Is wrong. Most Long Covid gets better before it qualifies as ME/CFS. 'POTS' is so vaguely defined, beyond orthosttic tachycardia, which may be normal, that it is absurd even to make this statement.

This is make believe quack medicine pure and simple.

 

[hotblack]

Hot off the press: my new paper that moves this field forward and changes the narrative on what #POTS, #MECFS and #LongCOVID are... Neuroimmune Disorders!

How can this move the field forward when there is (1) no new evidence, it’s a review and (2) no new ideas, just claims of things like neuroinflammation and t-cell exhaustion we’ve heard before.. Repeating something does not move a field forward. New evidence and new ideas do.

 

[DHagen]

None of these have been identified convincingly to my knowledge. Certainly nothing has been shown to be an 'important mechanistic factor' even if there are a few data showing differences from normals. The mechanisms are completely unknown.

Also:


Is wrong. Most Long Covid gets better before it qualifies as ME/CFS. 'POTS' is so vaguely defined, beyond orthosttic tachycardia, which may be normal, that it is absurd even to make this statement.

This is make believe quack medicine pure and simple.

Thank you for responding. I suppose I was just surprised at the casual and complete dismissal and was not reading "identified" to mean "proven," but that's on me. I was more focused on the neuroimmune claim, which I thought many here supported, at least as a likelihood.

Despite participating in some of the recent discussions on the topic, I also keep forgetting that everyone working on ME/CFS (save, what? Maybe 4 researchers?) practices "quack medicine."

Regardless, I recognize that, even if this paper's claims were 100% supported, it wouldn't get us anywhere and doesn't have anything new to offer - so I'll stop wasting time on the matter.

Thanks again for the clarification. I can imagine it must be exhausting to have so many people clamoring for comment and explanation (particularly when new people keep dropping in and out of the on-going conversation and you no doubt feel - quite rightly - your position has been made abundantly clear elsewhere). I appreciate your taking the time.

 

[Chandelier]

Svetlana disagrees.

Another lengthy tweet from her:

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I remember a time when senior colleagues were trying to convince me that POTS is about tachycardia and that these "other symptoms" of brain fog, headache and gastrointestinal symptoms are not from POTS, but from "comorbidities that are not POTS."​

I also remember a time when senior colleagues were telling me that the vast majority of POTS patients improve or recover 5-7 years after diagnosis.​

Or that many patients improve just with salt, fluids and compression.​

Or that teens with POTS outgrow it.​

Or that you can exercise your way out of it because astronauts returning from space develop gravity-induced orthostatic intolerance, and then, poof, come out of it with exercise.​

Over the last 2 decades of doing this work, I learned that I can now form my own opinions and not listen to what others are telling me because I have thousands of patients to back me up as my experience.​

Obviously, referral bias is strong for all of us as each of us may see a slightly different patient population, but the patterns are fairly the same.​

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Which brings me to this point: our understanding of #POTS, and patients with #dysautonomia who do not meet diagnostic criteria for POTS, is very much evolving.​

Sure, we like to have simplicity and think in black-and-white terms, but it's not like that with complex disorders.​

POTS is complex and is no longer viewed how we viewed it 30 years ago.​

Failing to reflect new insights and trying to keep the disorder simple and "how we always knew it" is failing to advance our understanding of these disorders and their treatment.​

Our recent review on POTS and other related disorders, which is still trending, highlights new insights and push for access to therapies that our patients cannot get.​

tandfonline.com/doi/full/10.…​

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[Jonathan Edwards]

POTS is complex and is no longer viewed how we viewed it 30 years ago.

Not sure what that means. Complex? Does that mean biopsychosocial? Or maybe just we don't understand it? I had never heard of POTS 30 years ago so hard to say about that.

What does it mean to be still trending I wonder?

 

[Chandelier]

What does it mean to be still trending I wonder?

The original tweet contained a screenshot of the popularity trend of that paper.

Unfortunately, xcancel has just gone down.
I guess that means no more Xcretion-news from me then.

On Monday 24th August at 8PM EST, we received at letter from X Corp. asking to cease and desist the service XCancel. The service XCancel is stopped until further notice. We are seeking legal advice and won't share more details for now. Thank you for the trust you have put in these two years of XCancel.

 

[Jonathan Edwards]

The original tweet contained a screenshot of the popularity trend of that paper.

How inane can you get?

 

[Chandelier]

How inane can you get?

The gamification of science.